Ryan C. Donohue

  • Adviser: Roberto Cattaneo, Ph.D.
  • Area of emphasis: Molecular virology
  • Research area: Intrahost genomic variation of measles virus

What are your research interests?

My interests are in understanding the evolutionary trajectory of a virus.

Small genome sizes, high replication capacity and error-prone replication machinery cause RNA viruses to be heterogeneous in infected hosts. Accumulation of mutations — whether beneficial, detrimental or neutral — gives rise to a unique assortment of viral genomic sequences that act cooperatively as a unit of selection, competition and variation. This mutant spectrum — known as a quasispecies — is ever changing, depending on the environment in which the virus is resident.

Because the pathogenesis of measles virus takes place in two major tissue types, measles virus is the ideal candidate to determine variation of quasispecies dynamics. My strategy for documenting differences in measles virus genomic variation is to adapt viruses to physiologically relevant cell lines by serial passaging, and then perform next-generation sequencing on tandem repeats of measles virus genome populations (CirSeq). This strategy filters out next-generation sequencing errors, allowing us to confidently determine low-frequency variants in an evolving viral population.

In examining fluctuations of mutants across cell types and passages, we can get a picture of areas in which the virus needs to keep conserved and areas in which the virus has more flexibility. We hope to discover novel regions of plastic protein surfaces that change depending on the cellular context in which the virus resides. This work will help to more accurately describe the evolutionary trajectory of a negative-strand RNA virus that still causes more than 100,000 deaths a year.

Why did you choose Mayo Clinic Graduate School of Biomedical Sciences' Virology and Gene Therapy track?

I chose to pursue a Ph.D. because I wanted to have access to all the tools necessary to realize my full potential as an independent scientist. After graduating from university, I worked as a technician, performing gene editing on soybeans to improve seed composition and generate a more productive crop. But, I desired more relevance to disease than plant editing could offer.

Mayo Clinic Graduate School of Biomedical Sciences' Virology and Gene Therapy track is a great fit to translate my gene editing background from plants to human disease.

Ironically, I chose a lab that focuses more on studying the molecular aspects of the viral life cycle rather than on gene or oncolytic virotherapy. Discovering the beautiful simplicity and molecular tricks of viruses has driven me to investigate how these intricacies work on the deepest level, and how we can manipulate them for our own good.

Once I gain a firm background in the science of viruses, I intend to use this knowledge for a more translational approach by developing virus-based therapies.

Honors and awards

  • Harry and Debra Stonecipher Predoctoral Fellowship, 2015-present
  • Graduate/Undergraduate Student Travel Grant to attend annual meeting, American Society for Virology, 2015
  • Participant (promoted funding of scientific research to Congress), Capitol Hill Day, American Society for Biochemistry and Molecular Biology, 2014
  • Dean's fellowship, 2013-2014

Leadership

  • Virology and Gene Therapy track representative, Mayo Clinic Graduate School of Biomedical Sciences' Student Association, 2014-2015
  • Co-president, Mayo Clinic Graduate School of Biomedical Sciences' Student Association, 2015-2016

Posters

  • Tissue-specific measles virus genome variation as virulence determinant. Poster presented at: American Society for Virology Annual Meeting; 2015; London, Ontario, Canada.
  • Tissue-specific measles virus genome variation as virulence determinant. Poster presented at: Institute for Molecular Virology Symposium; 2015; Minneapolis, Minn.
  • Tissue-specific measles virus genome variation as virulence determinant. Poster presented at: Mayo Clinic Graduate School of Biomedical Sciences Symposium; 2014; Rochester, Minn.

Affiliations

  • American Society for Biochemistry and Molecular Biology
  • American Society for Virology
Nov. 17, 2015